As a typical representative of Lepidopteran insects, the silkworm, Bombyx mori, has numerous advantages, such as simple husbandry,highly prolific nature, short generation time, easily handled to be operated with moderate body size, clear genetic background and abundant mutation resources. Silkworm has not only been studied by the geneticists, but also been used as a new laboratory animal model of human disease and drug screening. There is a plenty of genetic resources in silkworm, some of which could be used as models of human genetic diseases, such as Phenylketonuria, Parkinson’s disease, Hermansky-Pudlak syndrome and so on. Silkworm has also played a significant role in the study of pathogenesis of human pathogenic microorganisms. Moreover, silkworm could be used to evaluate the pharmacokinetic/pharmacodynamics properties and safety of a new drug comprehensively and systematically. At the same time, it can be used in the high throughput drug screening assays to shorten the period of the new drug research and development. This review summarizes that the silkworm is an excellent model in the drug screening assays, and has a potential in application to the large-scale drug screening.